Something to look forward to: Cancer has proven to be an extremely elusive target, with tumors developing resistance that allows them to sidestep drugs designed to treat them. However, a group of scientists has now devised a clever new strategy that turns cancer cells suicidal, forcing them to turn against each other.
The key innovation involves introducing two new “switches.” The first switch enables engineered cells to outgrow and dominate the rest of the cancer cell population when exposed to a particular drug. The second switch then unleashes a toxin that kills the now-dominant modified cells along with their unmodified neighbors.
This “dual switch selection gene drive” approach, as highlighted in a study published in Nature Biotechnology, tackles a core challenge with existing cancer treatments. Inevitably, some cancer cells evolve resistance mechanisms that allow them to survive therapy. Cells may inactivate drugs, turn off pathways the drugs target, or make other molecular changes to stay alive.
To counter this, doctors often use combinations of drugs that attack tumors in different ways. However, the options are limited, especially for hard-to-treat cancers where effective therapeutic targets are lacking.
The new technique takes a radically different approach. Instead of finding new drugs or targets, it exploits the tumor’s ability to rapidly evolve and uses that against it.
In their proof-of-concept experiments, the researchers used lung cancer cells and the drug erlotinib. Normally, erlotinib works by blocking the activation of the EGFR protein that drives uncontrolled cell growth. However, the scientists engineered lung cancer cells to reverse erlotinib’s effects through the first “suicide gene,” making the cells resistant and causing rapid proliferation when exposed to the drug.
Applying erlotinib to a mix of modified and unmodified cancer cells allowed the edited cells to quickly become the dominant population in the tumor sample. Once this was achieved, the researchers stopped administering the drug.
They then activated the second “suicide gene” using a harmless compound called 5-FC. This gene expressed an enzyme that converted 5-FC into the highly toxic anti-cancer drug 5-FU. With the edited cells now making up the bulk of the tumor, the released toxin effectively killed the entire cancer cell population.
Testing this approach in mice with non-small cell lung cancer, the most common lung cancer type, the researchers found the modified cells overtook the original tumors within 20 days. By day 80, the tumors had completely regressed.
The team is now working to test this approach on other cancer types and drug combinations. If it proves successful, it could provide a new way to outwit cancer.